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Reductant

Substrate

ADVANCED SYNTHESIS & CATALYSIS

Room temperature nickel(0)/tricyclohexylphosphine [Ni(0)/PCy3]-catalyzed Suzuki-Miyaura cross-couplings of 4-(p-toluenesulfonyloxy)coumarins and 4-(p-toluenesulfonyloxy)-2(5H)-furanone with arylboronic acids are described in this communcation. Our study shows that activated alkenyl tosylates possess higher activities than aryl tosylates in the Suzuki-Miyaura cross-couplings. The mild reaction conditions and the high efficiency of the Ni(0)/ PCy3 catalyst make it very useful in the synthesis of 4-substituted coumarins and 4-substituted 2(5H)-furanones, two families of biologically important molecules.

CUNY Coll Staten Isl

ADVANCED SYNTHESIS & CATALYSIS

We present a highly active, inexpensive, universally applicable, and markedly stable [1,3-bis(diphenylphosphino)propane]nickel(II) chloride [Ni(dppp)Cl-2] catalyst that is capable of effecting the Suzuki-Miyaura cross-coupling of the inherently less reactive but readily available aryl tosylates and mesylates with only 1 mol% loading and in the absence of extra supporting ligand. Under the optimized reaction conditions, cross-coupling of a wide range of activated, non-activated, and deactivated, as well as sterically hindered and heteroaromatic substrates (36 examples) could proceed efficiently to afford the coupled products in 53-99% yields. Consequently, the results presented in this work provide a significant advance in Suzuki-Miyaura cross-coupling in terms of generality, practicality, and cost which are key concerns in recent research regarding transition metal-catalyzed cross-couplings.

ADVANCED SYNTHESIS & CATALYSIS

Room temperature nickel(II) complexes [(4-MeOC6H4)Ni(PCy3)(2)OTs and Ni(PCy3)(2)X-2 (X=Cl, Br)]-catalyzed cross-coupling reactions of aryl/alkenyl sulfonates with arylboronic acids are described. The nickel(II) complex (4-MeOC6H4)Ni(PCy3)(2)OTs proved to be a general catalyst for the Suzuki-Miyaura cross-coupling reactions of aryl sulfonates with arylboronic acids. By limiting the amount of the water in the initial catalytically active Ni(0) species generation stage, Ni(PCy3)(2)X-2 (X=Cl, Br) could also be efficient catalysts for the cross-coupling reactions a variety of aryl/activated alkenyl tosylates with arylboronic acids. The mild reaction condition, the easy availability of the catalysts and excellent coupling yields make these catalyst systems potentially useful in organic synthesis.

ADVANCED SYNTHESIS & CATALYSIS

A new catalytic system for beta-alkylation of lactic acid with primary alcohols has been developed. In the presence of nickel(II) acetate tetrahydrate [Ni(OAc)(2)(H(2)O)(4)] and base, lactic acid reacts with primary alcohols to afford the corresponding coupled alpha-hydroxy carboxylic acids in good to excellent yields via a hydrogen transfer process without any hydrogen acceptor or hydrogen donor.

Rousseaux, SAL

J AM CHEM SOC

Herein, we report a Ni-catalyzed reductive coupling for the synthesis of benzonitriles from aryl (pseudo)halides and an electrophilic cyanating reagent, 2-methyl-2-phenyl malononitrile (MPMN). MPMN is a bench-stable, carbon-bound electrophilic CN reagent that does not release cyanide under the reaction conditions. A variety of medicinally relevant benzonitriles can be made in good yields. Addition of NaBr to the reaction mixture allows for the use of more challenging aryl electrophiles such as aryl chlorides, tosylates, and triflates. Mechanistic investigations suggest that NaBr plays a role in facilitating oxidative addition with these substrates.

Deaminative functionalization of aliphatic primary amines has great synthetic utility. Herein, we describe a Ni-catalyzed reductive deaminative cross-electrophile coupling reaction between Katritzky salts and aromatic amides. This work provides examples of the synthesis of various ketones from alkylpyridinium salts, including both primary and secondary alkylamines. Given its mild reaction conditions and high functional group tolerance, this cross-coupling strategy is expected to be useful for late-stage functionalization of complex compounds.

Univ Sci & Technol China

pyrrolidine-2,5-dione

2,4,6-Tris(4-Methoxyphenyl)Pyridinium+BF4-

Carbonyl

SYNTHESIS-STUTTGART

Cross-couplings of benzylic pyridinium salts and vinylboronic acids or esters have been developed. Via benzylic pyridinium intermediates, benzylic amines can be engaged in these cross-couplings through C-N bond functionalization. This method boasts mild reaction conditions and excellent tolerance for heteroaryl substituents and a range of functional groups.

Triphenylpyridinium+BF4-

ANGEW CHEM INT EDIT

This work bridges a gap in the cross-coupling of aliphatic redox-active esters with aryl zinc reagents. Previously limited to primary, secondary, and specialized tertiary centers, a new protocol has been devised to enable the coupling of general tertiary systems using nickel catalysis. The scope of this operationally simple method is broad, and it can be used to simplify the synthesis of medicinally relevant motifs bearing quaternary centers.

ADVANCED SYNTHESIS & CATALYSIS

2,4,6-Trichloro-1,3,5-triazine (TCT) was used as an efficient and mild reagent for the direct nickel-catalyzed amination of phenols. This reagent can promote amination of phenols via the activation of the phenolic C-O bond. In this simple protocol, the in situ generated aryl C-O electrophile (Ar-O-TCT) reacts with the desired amine to produce the corresponding arylamine in the presence of a nickel catalyst. This strategy is general for a variety of substrates to give the related arylamines in moderate to good yields. This method was also applied for nickel-catalyzed amination of phenols for the synthesis of primary aromatic amines using the reaction of Ar-O-TCT and ammonium carbonate under mild reaction conditions. With this method, phenolic compounds are converted to their corresponding anilines under mild conditions.

Morpholine

J AM CHEM SOC

The past decade has witnessed the rapid development of radical generation strategies and their applications in C-C bond-forming reactions. Most of these processes require initiators, transition metal catalysts, or organometallic reagents. Herein, we report the discovery of a simple organic system (2-azaallyl anions) that enables radical coupling reactions under transition-metal-free conditions. Deprotonation of N-benzyl ketimines generates semistabilized 2-azaallyl anions that behave as super-electron-donors (SEDs) and reduce aryl iodides and alkyl halides to aryl and alkyl radicals. The SET process converts the 2-azaallyl anions into persistent 2-azaallyl radicals, which capture the aryl and alkyl radicals to form C-C bonds. The radical coupling of aryl and alkyl radicals with 2-azaallyl radicals makes possible the synthesis of functionalized amine derivatives without the use of exogenous radical initiators or transition metal catalysts. Radical clock studies and 2-azaallyl anion coupling studies provide mechanistic insight for this unique reactivity.

Dankwardt, JW

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

New substrates for biaryl synthesis: aromatic ethers undergo nickel-catalyzed cross-coupling with aryl Grignard reagents to give unsymmetrical biaryls in excellent yields (see scheme). Both the nature of the nickel catalyst and the choice of solvent are crucial for reaching high levels of conversion.

DSM Pharmaceut Chem

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

To COMe and go: The title reaction, involving cleavage of a COMe bond, is demonstrated for the coupling of aryl methyl ethers on fused aromatic systems, such as naphthalene and phenanthrene, as well as anisoles containing electron-withdrawing groups with a wide range of boronic esters. cod=cycloocta-1,5-diene, Cy=cyclohexyl.

J AM CHEM SOC

Nickel-catalyzed intermolecular benzylation and heterobenzylation of unactivated alkenes to provide functionalized allylbenzene derivatives are described. A wide range of both the benzyl chloride and alkene coupling partners are tolerated. In contrast to analogous palladium-catalyzed variants of this process, all reactions described herein employ electronically unbiased aliphatic olefins (including ethylene), proceed at room temperature, and provide 1,1-disubstituted olefins over the more commonly observed 1,2-disubstituted olefins with very high selectivity.

ANGEW CHEM INT EDIT

Ecole Polytech Fed Lausanne

Direct catalytic alcoholysis of unactivated amides is one of the most difficult challenges in organic chemistry, and an applicable method for cleaving amides used as directing groups in regioselective functionalization reactions has not been reported. Herein, we report direct catalytic alcoholysis of 8-aminoquinoline amides, which are highly effective directing groups in regioselective functionalization reactions. The reactions proceeded with a simple combination of substrates, air-stable catalysts, and alcohols, affording the corresponding esters in good yields with broad functional group tolerance. Highly chemoselective cleavage of the 8-aminoquinoline amides in the presence of related Carbonyl functionalities and preliminary mechanistic studies are also described.

8-aminoquinoline

Carbonyl

Stradiotto, M

The Ni-catalyzed Csp2–N cross-coupling of NH substrates and (hetero)aryl (pseudo)halides for the synthesis of (hetero)anilines is in the midst of a resurgence. Reactivity breakthroughs that have been achieved in this field within the past five years have served to establish Ni catalysis as being competitive with, and in some cases superior to, more well-established Pd- or Cu-based protocols. Whereas the repurposing of useful ancillary ligands from the Pd domain has been the most frequently employed approach in the quest to develop effective Ni-based catalysts for such transformations, considerable progress has been made as of late in the design of ancillary ligands tailored specifically for use with Ni. Bisphosphine ancillary ligands have proven to be well-suited for such an approach, given their modular and facile syntheses; several variants have emerged recently that are particularly effective in enabling a range of otherwise challenging Ni-catalyzed Csp2–N cross-couplings. This Perspective presents a comprehensive summary of the advancements within the field of Ni-catalyzed Csp2–N cross-coupling through the application of the bisphosphine ancillary ligand class. It is our intention that the discussion of key ancillary ligand design concepts and mechanistic considerations presented herein will provide a useful platform for researchers to initiate ancillary ligand design efforts for the development of high-performing Ni cross-coupling catalysts.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Zhang, XJ; Zhang, GS

Alkynes are amongst the most valuable functional groups in organic chemistry and widely used in chemical biology, pharmacy, and materials science. However, the preparation of alkyl-substituted alkynes still remains elusive. Here, we show a nickel-catalyzed deaminative Sonogashira coupling of alkylpyridinium salts. Key to the success of this coupling is the development of an easily accessible and bench-stable amide-type pincer ligand. This ligand allows naturally abundant alkyl amines as alkylating agents in Sonogashira reactions, and produces diverse alkynes in excellent yields under mild conditions. Salient merits of this chemistry include broad substrate scope and functional group tolerance, gram-scale synthesis, one-pot transformation, versatile late-stage derivatizations as well as the use of inexpensive pre-catalyst and readily available substrates. The high efficiency and strong practicability bode well for the widespread applications of this strategy in constructing functional molecules, materials, and fine chemicals. Alkynes are amongst the most valuable functional groups in organic chemistry, however, the preparation of alkyl-substituted alkynes still remains elusive. Here the authors show a nickel-catalyzed deaminative Sonogashira coupling of alkylpyridinium salts.

Triphenylpyridinium+BF4-

Added by Imanuel

10.1039/d2gc00395c,10.1055/s-0040-1719881

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Morpholine

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Univ Calif Los Angeles

OSO2NMe2

Morpholine

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

O(Ring-Opening)

J AM CHEM SOC

The direct upgrading reaction of simple and readily available achiral alcohols via C-H functionalization is an ideal strategy to prepare value-added chiral higher alcohols. Herein, we disclose the first enantioconvergent upgrading reaction of simple racemic secondary alcohols to enantioenriched tertiary alcohols. An N-heterocyclic carbene (NHC)-nickel catalyst was leveraged to enable this highly efficient formal asymmetric alcohol alpha-C-H arylation via a dehydrogenation using phenyl triflate as a mild oxidant followed by asymmetric addition of arylboronic esters to the transient ketones. Mechanistic studies and control experiments were conducted to reveal the possible reasons for the exceptional control over chemo- and enantioselectivity.

Univ Chinese Acad Sci

We report details of the reaction mechanism for a coupling reaction of 1,3-dienes with C-nucleophiles that was catalyzed by a Ni/Cu cooperative catalyst system using Ni(cod)(2) and [Cu(CH3CN)(4)]PF6 in the presence of a chiral JOSIPHOS-type bisphosphine ligand and (Pr2NEt)-Pr-i, providing direct access to highly valuable vicinal quaternary and tertiary stereocenters with high enantio- and diastereoselectivity. The bimetallic cooperative catalyst system exhibited a broad substrate scope, including both cyclic/acyclic stabilized nucleophiles and aryl-/alkyl-substituted 1,3-dienes. The bimetallic cooperative catalyst mechanism was elucidated in depth by isolating and characterizing four key complexes of nickel and copper and conducting deuterium labeling experiments, kinetic studies, and density functional theory calculations. The turnover-limiting step of this reaction is the proton-transfer step to diene-coordinated Ni complex 6 from cationic Cu complex 8 to yield p-allyl Ni complex 7 and Cu enolate complex 9, respectively. The stereoselectivity of the reaction was also clarified according to single-point calculations of the key intermediates 7 and 9.

J AM CHEM SOC

The use of a simple stilbene ligand has enabled a stereospecific Suzuki-Miyaura cross-coupling of tertiary benzylic carboxylates, including those lacking naphthyl substituents. This method installs challenging all-carbon diaryl quaternary stereocenters in good yield and ee and represents an important breakthrough in the naphthyl requirement that pervades stereospecific cross-couplings involving enantioenriched electrophiles.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

OCCOMe

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Achieving high selectivity in the Heck reaction of electronically unbiased alkenes has been a longstanding challenge. Using a nickel-catalyzed cationic Heck reaction, we were able to achieve excellent selectivity for branched products (19:1 in all cases) over a wide range of aryl electrophiles and aliphatic olefins. A bidentate ligand with a suitable bite angle and steric profile was key to obtaining high branched/linear selectivity, whereas the appropriate base suppressed alkene isomerization of the product. Although aryl triflates are traditionally used to access the cationic Heck pathway, we have shown that, by using triethylsilyl trifluoromethanesulfonate, we can effect a counterion exchange of the catalytic nickel complex, such that cheaper and more stable aryl chlorides, mesylates, tosylates, and sulfamates can be used to yield the same branched products with high selectivity.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Alkyl Grignard reagents that contain beta-hydrogen atoms were used in a stereospecific nickel-catalyzed cross-coupling reaction to form C(sp(3))-C(sp(3)) bonds. Aryl Grignard reagents were also utilized to synthesize 1,1-diarylalkanes. Several compounds synthesized by this method exhibited selective inhibition of proliferation of MCF-7 breast cancer cells.

ANGEW CHEM INT EDIT

We report a means to achieve the addition of two disparate nucleophiles to the amide Carbonyl carbon in a single operational step. Our method takes advantage of non-precious-metal catalysis and allows for the facile conversion of amides to chiral alcohols via a one-pot Suzuki-Miyaura cross-coupling/transfer-hydrogenation process. This study is anticipated to promote the development of new transformations that allow for the conversion of carboxylic acid derivatives to functional groups bearing stereogenic centers via cascade processes.

Univ Calif Los Angeles

N(Bn)Boc

Carbonyl

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

The direct replacement of aromatic methoxy groups with activated carbon nucleophiles would give rise to novel synthetic pathways for targeted and diversity-oriented syntheses. We demonstrate here that this transformation can be achieved in a one-step reaction involving a bifunctional organolithium nucleophile in combination with a C-Ar-OMe bond-cleaving nickel catalyst. The resulting products are stable, alpha-CH active, and suitable for various further modifications.

Rhein Westfal TH Aachen

Csp3-Si

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

The nickel-catalyzed alpha-arylation of ketones with readily available phenol derivatives (esters and carbamates) provides access to useful alpha-arylketones. For this transformation, 3,4-bis(dicyclohexylphosphino)thiophene (dcypt) was identified as a new, enabling, air-stable ligand for this transformation. The intermediate of an assumed C-O oxidative addition was isolated and characterized by X-ray crystal-structure analysis.

Stradiotto, M

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Structurally diverse (hetero)aryl chloride, bromide, and tosylate electrophiles were employed in the Ni-catalyzed monoarylation of ammonia, including chemoselective transformations. The employed JosiPhos/[Ni(cod)(2)]catalyst system enables the use of commercially available stock solutions of ammonia, or the use of ammonia gas in these reactions, thereby demonstrating the versatility and potential scalability of the reported protocol. Proof-of-principle experiments established that air-stable [(JosiPhos)NiCl2] precatalysts can be employed successfully in such transformations.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

We report the first enantioselective C-C bond formation through C-O bond cleavage using aryl ester counterparts. This method is characterized by its wide substrate scope and results in the formation of quaternary stereogenic centers with high yields and asymmetric induction.

Inst Chem Res Catalonia ICIQ

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

A new substrate class for nickel-catalyzed C(sp(3)) cross-coupling reactions is reported. alpha-Oxy radicals generated from benzylic acetals, TMSCl, and a mild reductant can participate in chemoselective cross-coupling with aryl iodides using a 2,6-bis(N-pyrazolyl)pyridine (bpp)/Ni catalyst. The mild, base-free conditions are tolerant of a variety of functional groups on both partners, thus representing an attractive C-C bond-forming approach to dialkyl ether synthesis. Characterization of a [(bpp)NiCl] complex relevant to the proposed catalytic cycle is also described.

Csp3-(Aryl)(OR)

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Palladium-catalyzed allylic substitution reactions are among the most efficient methods to construct C-C bonds between sp(3)-hybridized carbon atoms. In contrast, much less work has been done with nickel catalysts, perhaps because of the different mechanisms of the allylic substitution reactions. Palladium catalysts generally undergo substitution by a soft-nucleophile pathway, wherein the nucleophile attacks the allyl group externally. Nickel catalysts are usually paired with hard nucleophiles, which attack the metal before C-C bond formation. Introduced herein is a rare nickel-based catalyst which promotes substitution with diarylmethane pronucleophiles by the soft-nucleophile pathway. Preliminary studies on the asymmetric allylic alkylation are promising.

A modular method for the acylation of aryl and alkyl halides is reported herein. The transformation relies on acylimidazoles, easy-to-prepare and flexible species derived from abundant carboxylic acids, as viable cross-coupling partners for the Ni-catalyzed acylation. Careful examination revealed a remarkable mechanism: the amide C-N bond of primary and secondary imidazolides can be activated by single-electron reduction, representing a major departure from other reported amide C-N bond activation reactions. Extensive mechanistic studies also revealed an intriguing CO-extrusion-recombination phenomenon. This cross-coupling reaction between two electrophiles features a broad substrate scope bearing a wide gamut of functionalities. The practicality of this atypical transformation was demonstrated in the syntheses of 3-furyl natural products, which are difficult to access using traditional organometallic chemistry.

Peking Union Med Coll & Chinese Acad Med Sci

Carbonyl

Nickel complexes bearing chiral diphosphine ligands, such as (S)-Tol-MeO-BIPHEP and (S)-H-8-BINAP, serve as efficient catalysts for asymmetric allylic alkylation (AAA) of beta-ketoesters, using allylic amines as ally! sources. The reactions proceed with high catalytic activity and high enantioselectivity. N-Methyl-N-phenyl allylic amines were indispensable to achieve the high catalytic activity, to achieve the high enantioselectivity, and to expand the substrate scope to 5- and 7-membered beta-ketoesters, whose nickel-catalyzed AAA with allylic alcohols results in low enantioselectivity. On the basis of the kinetics using a catalyst system made of Ni(cod)(2) and (S)-Tol-MeO-BIPHEP, and DFT calculations for the reaction pathway of the AAA reaction mediated by an isolated olefin-coordinated nickel-DPPF complex 4b, we propose a mechanism where protonation of the nitrogen atom of the coordinating allylic amine by beta-ketoester is key to cleaving the C-N bond and delivering a cationic pi-allyl nickel(II) intermediate.

Shanghai Jiao Tong Univ

N(Me)Ph

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Asymmetric allylic alkylation of -ketoesters with allylic alcohols catalyzed by [Ni(cod)(2)]/(S)-H-8-BINAP was found to be a superior synthetic protocol for constructing quaternary chiral centers at the -position of -ketoesters. The reaction proceeded in high yield and with high enantioselectivity using various -ketoesters and allylic alcohols, without any additional activators. The versatility of this methodology for accessing useful and enantioenriched products was demonstrated.

Herein, we report a nickel-1,2-bis-(dicyclohexylphosphino)ethane (dcype) complex for the catalytic Buchwald-Hartwig amination of aryl thioethers. The protocol shows broad applicability with a variety of different functional groups tolerated under the catalytic conditions. Extensive organo-metallic and kinetic studies support a nickel(0)-nickel(II) pathway for this transformation and revealed the oxidative addition complex as the resting state of the catalytic cycle. All the isolated intermediates have proven to be catalytically and kinetically competent catalysts for this transformation. The fleeting transmetalation intermediate has been successfully synthesized through an alternative synthetic organometallic pathway at lower temperature, allowing for in situ NMR study of the C-N bond reductive elimination step. This study addresses key factors governing the mechanism of the nickel-catalyzed Buchwald-Hartwig amination process, thus improving the understanding of this important class of reactions.

Swiss Fed Inst Technol

Morpholine

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

In the presence of trialkylaluminum reagents, diverse aryl methyl ethers can be transformed into valuable products by C-O bond-cleaving alkylation, for the first time without the limiting -hydride elimination. This new nickel-catalyzed dealkoxylative alkylation method enables powerful orthogonal synthetic strategies for the transformation of a variety of naturally occurring and easily accessible anisole derivatives. The directing and/or activating properties of aromatic methoxy groups are utilized first, before they are replaced by alkyl chains in a subsequent coupling process.

Rhein Westfal TH Aachen

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Using nickel and photoredox catalysis, the direct functionalization of C(sp(3))-H bonds of N-aryl amines by acyl electrophiles is described. The method affords a diverse range of -amino ketones at room temperature and is amenable to late-stage coupling of complex and biologically relevant groups. C(sp(3))-H activation occurs by photoredox-mediated oxidation to generate -amino radicals which are intercepted by nickel in catalytic C(sp(3))-C coupling. The merger of these two modes of catalysis leverages nickel's unique properties in alkyl cross-coupling while avoiding limitations commonly associated with transition-metal-mediated C(sp(3))-H activation, including requirements for chelating directing groups and high reaction temperatures.

Carbonyl

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

We report the first catalytic method for activating the acyl C-O bonds of methyl esters through an oxidative-addition process. The oxidative-addition adducts, formed using nickel catalysis, undergo in situ trapping to provide anilide products. DFT calculations are used to support the proposed reaction mechanism, to understand why decarbonylation does not occur competitively, and to elucidate the beneficial role of the substrate structure and the Al(OtBu)(3) additive on the kinetics and thermodynamics of the reaction.

Univ Calif Los Angeles

Carbonyl

N(Alkyl)Aryl

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Nickel-catalyzed cross-electrophile coupling reactions of benzylic esters and aryl halides have been developed. Both inter-and intramolecular variants proceed under mild reaction conditions. A range of heterocycles and functional groups are tolerated under the reaction conditions. Additionally, the first example of a stereospecific cross-electrophile coupling of a secondary benzylic ester is described.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

A nickel-catalyzed alkylation of polycyclic aromatic methyl ethers as well as methyl enol ethers with B-alkyl 9-BBN and trialkylborane reagents that involves the cleavage of stable C(sp(2))-OMe bonds is described. The transformation has a wide substrate scope and good chemoselectivity profile while proceeding under mild reaction conditions; it provides a versatile way to form C(sp(2))-C(sp(3)) bonds that does not suffer from -hydride elimination. Furthermore, a selective and sequential alkylation process by cleavage of inert C-O bonds is presented to demonstrate the advantage of this method.

Rhein Westfal TH Aachen

TETRAHEDRON

The cross-coupling of aryltrimethylammonium triflates with AIMe(3) and beta-H-containing trialkylaluminums was performed in dioxane at 110 C-omicron under catalysis of (dPPP)NiCl2 to afford alkylated arenes. The cross-coupling of 2-menaphthyltrimethylammonium triflate with trialkylaluminums and 1-naphthyltrimethylammonium triflate with triarylaluminums was also carried out respectively under the same conditions. (C) 2017 Elsevier Ltd. All rights reserved.

Univ Sci & Technol China

NMe3+OTf-

ANGEW CHEM INT EDIT

Cross-hydroalkenylation of a vinyl ether (1) with an -olefin (2) was first achieved by a set of [NHC-Ni(allyl)]BArF (NHC=N-heterocyclic carbene) catalysts. Both 1,2- and 1,3-disubstituted allyl ethers were obtained, highly selectively, by using NHCs of different sizes. In contrast, the chemoselectivity (i.e., 1 as acceptor and 2 as donor) was controlled mostly by electronic effects through the catalyst-substrate interaction. Sterically bulkier alkenes (2) were used as preferred donors compared to smaller alkenes. This electronic effect also served as a basis for the first tail-to-head cross-hydroalkenylations of 1 with either a vinyl silane or boronic ester.

Southern Univ Sci & Technol SUSTech

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

The enantioselective desymmetrization of cyclic meso-anhydrides with benzyl trifluoroborates under nickel-photoredox catalysis is described. The reaction tolerates a variety of sterically and electronically different trifluoroborates, as well as structurally unique cyclic anhydrides. The trans isomer of the keto-acid products is also observed at varying levels dependent on the trifluoroborate identity and relative catalyst loading. A mechanism involving decarbonylation and Ni-C bond homolysis of a Ni-II adduct is proposed. This feature allows access to a trans keto-acid as the major product in high enantioselectivity from a cis meso anhydride.

O(Ring-Opening)

ORG BIOMOL CHEM

Nickel-catalyzed alpha-arylation of ketones involving aromatic C-N cleavage has been accomplished. Inter-molecular coupling of aromatic ketones with a variety of aryltrimethylammonium triflates was achieved in the presence of Ni(COD)(2), IPr center dot HCl, and LiOBut, giving alpha-arylated ketones in reasonable to excellent yields.

Univ Sci & Technol China

Triphenylpyridinium+BF4-

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

The construction of all C(sp(3)) quaternary centers has been successfully achieved under Ni-catalyzed cross-electrophile coupling of allylic carbonates with unactivated tertiary alkyl halides. For allylic carbonates bearing C1 or C3 substituents, the reaction affords excellent regioselectivity through the addition of alkyl groups to the unsubstituted allylic carbon terminus. The allylic alkylation method also exhibits excellent functional-group compatibility, and delivers the products with high Eselectivity.

OCO2Me

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

The use of transition-metal catalysis to enable the coupling of readily available organic molecules has greatly enhanced the ability of chemists to access complex chemical structures. In this work, an intermolecular coupling reaction that unites organotriflates and aldehydes is presented. A unique catalyst system is identified to enable this reaction, featuring a Ni-0 precatalyst, a tridentate Triphos ligand, and a bulky amine base. This transformation provides access to a variety of ketone-containing products without the selectivity- and reactivity-related challenges associated with more traditional Friedel-Crafts reactions. A Heck-type mechanism is postulated, wherein the bond of the aldehyde takes the role of the olefin in the insertion/elimination steps.

Carbonyl

Carbonyl

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

The incorporation of C-glycosides in drug design has become a routine practice for medicinal chemists. These naturally occurring building blocks exhibit attractive pharmaceutical profiles, and have become an important target of synthetic efforts in recent decades.([1]) Described herein is a practical, scalable, and versatile route for the synthesis of non-anomeric and unexploited C-acyl glycosides through a Ni/photoredox dual catalytic system. By utilizing an organic photocatalyst, a range of glycosyl-based radicals are generated and efficiently coupled with highly functionalized carboxylic acids at room temperature. Distinctive features of this transformation include its mild conditions, impressive compatibility with a wide array of functional groups, and most significantly, preservation of the anomeric carbon: a handle for further, late-stage derivatization.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

The preparation of allylic amines is traditionally accomplished by reactions of amines with reactive electrophiles, such as allylic halides, sulfonates, or oxyphosphonium species; such methods involve hazardous reagents, generate stoichiometric waste streams, and often suffer from side reactions (such as overalkylation). We report here the first broad-scope nickel-catalysed direct amination of allyl alcohols: An inexpensive Ni-II/Zn couple enables the allylation of primary, secondary, and electron-deficient amines without the need for glove-box techniques. Under mild conditions, primary and secondary aliphatic amines react smoothly with a range of allyl alcohols, giving secondary and tertiary amines efficiently. This totally catalytic method can also be applied to electron-deficient nitrogen nucleophiles; the practicality of the process was demonstrated in an efficient, gram-scale preparation of the calcium antagonist drug substance flunarizine (Sibelium (R)).

N(Alkyl)Alkyl

Montgomery, J

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Silyloxyarenes were utilized as electrophilic coupling partners with amines in the synthesis of aniline derivatives. A diverse range of amine substrates were used, including cyclic or acyclic secondary amines, secondary anilines, and sterically hindered primary anilines. Additionally, a range of sterically hindered and unhindered primary aliphatic amines were employed, which have previously been challenging with other classes of aryl ether electrophiles. Orthogonal couplings of silyloxyarenes with aryl methyl ethers are illustrated, where selectivity between the two C-O electrophiles is determined by ligand control, thereby allowing complementary and selective late-stage diversification of either electrophile. Finally, a sequential coupling displays the utility of this amination method along with the reversal in intrinsic reactivity between aryl methyl ethers and silyloxyarenes.

OSi(tBu)Me2

Morpholine

We report a strategy that combines alkene hydroacylation and enantioselective alpha-(hetero)arylation reactions to form a wide variety of nitrogen-containing heterocyclic ketones bearing alpha-chiral quaternary stereogenic centers. Exo-selective, intramolecular Ni-catalyzed hydroacylations of N-homoallylindole- and N-homoallylpyrrole-2-carboxaldehydes form alpha-substituted six-membered heterocyclic ketones in up to 95% yield, while N-heterocyclic carbene (NHC) catalyzed hydroacylations of N-allylindole- and N-allylpyrrole-2-carboxaldehydes form alpha-substituted five-membered heterocyclic ketones in up to 99% yield. The racemic five- and six-membered products of Ni- and NHC-catalyzed hydroacylation reactions are readily transformed into heterocyclic ketones containing an alpha-chiral quaternary stereogenic center by enantioselective Ni-catalyzed alpha-arylation and alpha-heteroarylation reactions. The chiral, nonracemic products formed through a combination of alkene hydroacylation and alpha-(hetero)arylation reactions are formed in moderate to high yields (4499%) with excellent enantioselectivities (typically >95% ee). The identity of the precatalyst for Ni-catalyzed alpha-(hetero)arylation is dictated by the identity of the alpha-substituted heterocyclic ketone starting material. alpha-(Hetero)arylations of six-membered heterocyclic ketones occur at 65-85 C in the presence of a catalyst generated in situ from Ni(COD)(2) and (R)-BINAP or (R)-DIFLUORPHOS. alpha-(Hetero)arylation of five-membered heterocyclic ketones must be conducted at room temperature in the presence of an [((R)-BINAP)Ni(eta(2)-NC-Ph)] precatalyst or a catalyst generated in situ from Ni(COD)(2), (R)-DIFLUORPHOS, and benzonitrile.

Nickel-catalyzed regioselective C-H bond alkenylation of indoles and related heteroarenes with alkenyl bromides is accomplished under relatively mild conditions. This method allows the straightforward synthesis of C-2 alkenylated indoles employing an air-stable and well-defined nickel catalyst, (bpy)NiBr2, providing a solution to the limitations associated with hydroindolation and oxidative alkenylation. The reaction conceded the coupling of indole derivatives with various alkenyl bromides, such as aromatic and heteroaromatics, alpha- and beta-substituted as well as exo- and endo-cyclic alkenyl compounds. An extensive mechanistic investigation, including controlled study, reactivity experiments, kinetics and labeling studies, and EPR and XPS analyses, highlights that the alkenylation proceeds through a single-electron transfer process comprising an odd-electron oxidative addition of alkenyl bromide. Furthermore, the alkenylation operates via a probable Ni(I)/Ni(III) pathway involving the rate-limiting C-H nickelation of indole.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Despite being one of the most important and frequently run chemical reactions, the synthesis of amide bonds is accomplished primarily by wasteful methods that proceed by stoichiometric activation of one of the starting materials. We report a nickel-catalyzed procedure that can enable diverse amides to be synthesized from abundant methyl ester starting materials, producing only volatile alcohol as a stoichiometric waste product. In contrast to acid- and base-mediated amidations, the reaction is proposed to proceed by a neutral cross coupling-type mechanism, opening up new opportunities for direct, efficient, chemoselective synthesis.

Carbonyl

Morpholine

An efficient nickel-catalyzed cyanation of aryl sulfonates, fluorosulfonates, and sulfamates with Zn(CN)(2) was developed, which provides a facile access to the nitrile products in generally good to excellent yields. The reaction is accomplished by using Ni-II complex as the precatalyst and DMAP as the additive. The method also displays wide functional group compatibility; for example, keto, methoxy, N,N-dimethylamino, cyano, ester, and pyridyl groups are well-tolerated during the reaction process.

A mild and efficient nickel-catalyzed method for the coupling of unactivated primary and secondary alkyl chlorides with the C-H bond of indoles and pyrroles is described which demonstrates a high level of chemo and regioselectivity. The reaction tolerates numerous functionalities, such as halide, alkenyl, alkynyl, ether, thioether, furanyl, pyrrolyl, indolyl and carbazolyl groups including acyclic and cyclic alkyls under the reaction conditions. Mechanistic investigation highlights that the alkylation proceeds through a single-electron transfer (SET) process with Ni(i)-species being the active catalyst. Overall, the alkylation follows a Ni(i)/Ni(iii) pathway involving the rate-influencing two-step single-electron oxidative addition of alkyl chlorides.

CHEM COMMUN

Herein is reported the mild and general coupling of amine/ether C(sp(3))-H bonds with various kinds of C(sp(2))-O electrophiles with high selectivity and efficiency. Valuable allylic/benzylic amines are generated in moderate to excellent yields. The utility of this transformation is demonstrated by a broad substrate scope (> 50 examples), good functional group tolerance and facile product modification.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

A regioselective, nickel-catalyzed photoredox allylation of secondary, benzyl, and alpha-alkoxy radical precursors is disclosed. Through this manifold, a variety of linear allylic alcohols and allylated monosaccharides are accessible in high yields under mild reaction conditions. Quantum mechanical calculations [DET and DLPNO-CCSD(T)/support the mechanistic hypothesis of a Ni-0 to Ni-11 oxidative addition pathway followed by radical addition and inner-sphere allylation.

O(Ring-Opening)

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

A stereodivergent reductive coupling reaction between allylic carbonates and vinyl triflates to furnish both E- and Z-configured 1,4-dienes has been achieved by visible-light-induced photoredox/nickel dual catalysis. The mild reaction conditions allow good compatibility of both vinyl triflates and allylic carbonates. Notably, the stereoselectivity of this synergistic cross-electrophile coupling can be tuned by an appropriate photocatalyst with a suitable triplet-state energy, providing a practical and stereodivergent means to alkene synthesis. Preliminary mechanistic studies shed some light on the coupling step as well as the control of the stereoselectivity step.

J AM CHEM SOC

Enabled by nickel catalysis, a mild and general catalytic method for C-alkylation of nitroalkanes with unactivated alkyl iodides is described. Compatible with primary, secondary, and tertiary alkyl iodides; and tolerant of a wide range of functional groups, this method allows rapid access to diverse nitroalkanes.

ANGEW CHEM INT EDIT

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Photochemical enantioselective nickel-catalyzed cross-coupling reactions are difficult to implement. We report a visible-light-mediated strategy that successfully couples symmetrical anhydrides and 4-alkyl dihydropyridines (DHPs) to afford enantioenriched alpha-substituted ketones under mild conditions. The chemistry does not require exogenous photocatalysts. It is triggered by the direct excitation of DHPs, which act as a radical source and as a reductant, facilitating the turnover of the chiral catalytic nickel complex.

Carbonyl

Cross couplings between simple allylic alcohols and aryl and vinyl boronic acids are efficiently catalyzed by nickel(0) catalysts and bidentate N-heterocyclic carbene/phosphine ligands. The bidentate nature of the ligand is shown to extend catalyst lifetime and enable high yields of the corresponding cross-coupling products. X-ray crystallography confirms the bidentate nature of the ligand scaffold. Multistep cross coupling-alkene/alkyne insertions reactions are also conducted and the bidentate nature of the substrate makes the pendant phosphine of the ligand unnecessary.

Stradiotto, M

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

The development of Ni-catalyzed C-N cross-couplings of sulfonamides with (hetero)aryl chlorides is reported. These transformations, which were previously achievable only with Pd catalysis, are enabled by use of air-stable (L)NiCl(o-tol) pre-catalysts (L=PhPAd-DalPhos and PAd2-DalPhos), without photocatalysis. The collective scope of (pseudo)halide electrophiles (X=Cl, Br, I, OTs, and OC(O)NEt2) demonstrated herein is unprecedented for any reported catalyst system for sulfonamide C-N cross-coupling (Pd, Cu, Ni, or other). Preliminary competition experiments and relevant coordination chemistry studies are also presented.

OCONEt2

NHSO2R

A nickel-catalyzed Kumada coupling of aniline derivatives was developed by selective cleavage of aryl C-N bonds under mild reaction conditions. Without preinstallation of an ortho directing group on anilines, the cross-coupling reactions of Boc-protected aromatic amines with aryl Grignard reagents afforded unsymmetric biaryls. Mechanistic studies by DFT calculations revealed that the nickel-mediated C-N bond cleavage is the rate-limiting step.

Univ Chinese Acad Sci

N(Ph)Boc

ORGANOMETALLICS

The quinoline-based pincer nickel(II) complexes kappa(N),kappa(N),kappa(N) -{R2N-C6H4-(mu-N)-C9H6N}NiX (((NNNQ)-N-R2)NiCl: R = Me) 2a; R = Et, 2b) were synthesized by the reaction of the ligand precursors ((NNNQ)-N-R2)H (R = Me, 1a; R = Et, 1b) with (DME)NiCl2 in the presence of Et3N. Similarly, the pincer mickel(II) derivatives ((NNNQ)-N-R2)NiX (R = Me, X = Br, 3a; R = Et, X = Br, 3b; R = Me, X = OAc, 4a) were obtained by treatment of the ligands ((NNNQ)-N-R2)H with the nickel precursor (THF)(2)NiBr2 or Ni(QAc)(2). All of these complexes were characterized by H-1 and C-13 NMR spectroscopy as well as by elemental analysis. Further, the molecular structures of 2a and 3a,b were elucidated by X-ray crystallography. Complex 2a is found to be an efficient catalyst for the direct C-H bond alkylation of substituted benzothiazoles and oxazoles with various unactivated alkyl halides containing beta-hydrogens under mild reaction conditions. The catalyst 2a is very robust and was recycled and reused five times for the alkylation reaction without a decrease in its catalytic activity. Preliminary studies reveal that the catalyst 2a acts as an active catalyst and the alkylation reaction appears to operate via a radical pathway.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

The increasing pharmaceutical importance of trifluoromethylarenes has stimulated the development of more efficient trifluoromethylation reactions. Tremendous efforts have focused on copper- and palladium-mediated/catalyzed trifluoromethylation of aryl halides. In contrast, no general method exists for the conversion of widely available inert electrophiles, such as phenol derivatives, into the corresponding trifluoromethylated arenes. Reported herein is a practical nickel-mediated trifluoromethylation of phenol derivatives with readily available trimethyl(trifluoromethyl)silane (TMSCF3). The strategy relies on PMe3-promoted oxidative addition and transmetalation, and CCl3CN-induced reductive elimination. The broad utility of this transformation has been demonstrated through the direct incorporation of trifluoromethyl into aromatic and heteroaromatic systems, including biorelevant compounds.

EUR J ORG CHEM

The direct decarboxylative arylation of hetereoarenes with benzoic acids through a nickel-catalyzed sp(2) C-H functionalization process was developed. This process provides the first examples of decarboxylative cross-coupling reactions with aromatic acids through nickel catalysis and tolerates a variety of functional groups. Moreover, this method provides efficient access to 2-aryl-substituted azoles, an important structural unit in natural products, medicinal compounds, and functional materials.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

The challenging nickel-catalyzed mono-alpha-arylation of acetone with aryl chlorides, pivalates, and carbamates has been achieved for the first time. A nickel/Josiphos-based catalytic system is shown to feature unique catalytic behavior, allowing the highly selective formation of the desired mono-alpha-arylated acetone. The developed methodology was applied to a variety of (hetero)aryl chlorides including biologically relevant derivatives. The methodology has been extended to the unprecedented coupling of acetone with phenol derivatives. Mechanistic studies allowed the isolation and characterization of key Ni(0)and Ni(II)catalytic intermediates. The Josiphos ligand is shown to play a key role in the stabilization of Ni(II)intermediates to allow a Ni-0/Ni(II)catalytic pathway. Mechanistic understanding was then leveraged to improve the protocol using an air-stable Ni(II)pre-catalyst.

Carbonyl

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Nickel-catalyzed intermolecular Heck reaction of cycloalkenes proceeds well with aryl triflates, mesylates and tosylates in excellent enantiomeric ratios. The asymmetric reductive Heck reaction also works with a 2-cyclopentenone ketal, which is equivalent to conjugate arylation of the enone itself.

Nanyang Technol Univ

Stradiotto, M

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

The Ni-catalyzed N-arylation of beta-fluoroalkylamines with broad scope is reported for the first time. Use of the air-stable pre-catalyst (PAd2-DalPhos)Ni(o-tol)Cl allows for reactions to be conducted at room temperature (25 degrees C, NaOtBu), or by use of a commercially available dual-base system (100 degrees C, DBU/NaOTf), to circumvent decomposition of the N-(beta-fluoroalkyl)aniline product. The mild protocols disclosed herein feature broad (hetero)aryl (pseudo)halide scope (X=Cl, Br, I, and for the first time phenol-derived electrophiles), encompassing base-sensitive substrates and enantioretentive transformations, in a manner that is unmatched by any previously reported catalyst system.

N(H)Alkyl

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

The direct conversion of alkyl esters to ketones has been hindered by the sluggish reactivity of the starting materials and the susceptibility of the product towards subsequent nucleophilic attack. We have now achieved a cross-coupling approach to this transformation using nickel, a bulky N-heterocyclic carbene ligand, and alkyl organoboron coupling partners. 65 alkyl ketones bearing diverse functional groups and heterocyclic scaffolds have been synthesized with this method. Catalyst-controlled chemoselectivity is observed for C(acyl)-O bond activation of multi-functional substrates bearing other bonds prone to cleavage by Ni, including aryl ether, aryl fluoride, and N-Ph amide functional groups. Density functional theory calculations provide mechanistic support for a Ni-0/Ni-II catalytic cycle and demonstrate how stabilizing non-covalent interactions between the bulky catalyst and substrate are critical for the reaction's success.

Carbonyl

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Canonical nucleosides are vulnerable to enzymatic and chemical degradation, yet their stable mimics-C-aryl nucleosides-have demonstrated potential utility in medicinal chemistry, chemical biology, and synthetic biology, although current synthetic methods remain limited in terms of scope and selectivity. Herein, we report a cross-electrophile coupling to prepare C-aryl nucleoside analogues from readily available furanosyl acetates and aryl iodides. This nickel-catalyzed modular approach is characterized by mild reaction conditions, broad substrate scope, excellent beta-selectivity, and high functional-group compatibility. The exclusive chemoselectivity with respect to the aryl iodide enables efficient preparation of a variety of C-aryl halide furanosides suitable for various downstream transformations. The practicality of this transformation is demonstrated through the synthesis of a potent analogue of a naturally occurring NF-kappa B activator.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Catalytic alkylation of stable alkenyl C-O electrophiles is synthetically appealing, but studies to date have typically focused on the reactions with alkyl Grignard reagents. We report herein a cross-electrophile reaction of alkenyl acetates with alkyl bromides. This work has enabled a new method for the synthesis of aliphatic alkenes from alkenyl acetates to be established that can be used to add more structural complexity and molecular diversity with enhanced functionality tolerance. The method allows for a gram-scale reaction and modification of biologically active molecules, and it affords access to useful building blocks. Preliminary mechanistic studies reveal that the Ni-I species plays an essential role for the success of the coupling of these two reactivity-mismatched electrophiles.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

A method was developed for ketone synthesis via a photoredox-assisted reductive acyl cross-coupling (PARAC) using a nickel/photoredox dual-catalyzed cross-electrophile coupling of two different carboxylic acid esters. A variety of aryl, 1 degrees, 2 degrees, 3 degrees-alkyl 2-pyridyl esters can act as acyl electrophiles while N-(acyloxy)phthalimides (NHPI esters) act as 1 degrees, 2 degrees, 3 degrees-radical precursors. Our PARAC strategy provides an alternative and reliable way to synthesize various sterically congested 3 degrees-3 degrees, 3 degrees-2 degrees, and aryl-3 degrees ketones under mild and highly unified conditions, which have been otherwise difficult to access. The combined experimental and computational studies identified a Ni-0/Ni-I/Ni-III pathway for ketone formation.

Carbonyl

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Here we report a practical, highly enantioselective photoredox allylation of aldehydes mediated by chiral nickel complexes with commercially available allyl acetate as the allylating agent. The methodology allows the clean stereoselective allylation of aldehydes in good to excellent yields and up to 93 % e.e. using a catalytic amount of NiCl2(glyme) in the presence of the chiral aminoindanol-derived bis(oxazoline) as the chiral ligand. The photoredox system is constituted by the organic dye 3DPAFIPN and a Hantzsch's ester as the sacrificial reductant. The reaction proceeds under visible-light irradiation (blue LEDs, 456 nm) at 8-12 degrees C. Compared to other published procedures, no metal reductants (such as Zn or Mn), additives (e.g. CuI) or air-sensitive Ni(COD)(2) are necessary for this reaction. Accurate DFT calculations and photophysical experiments have clarified the mechanistic picture of this stereoselective allylation reaction.

Carbonyl

Stradiotto, M

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

The C-N cross-coupling of (hetero)aryl (pseudo)halides with NH substrates employing nickel catalysts and organic amine bases represents an emergent strategy for the sustainable synthesis of (hetero)anilines. However, unlike protocols that rely on photoredox/electrochemical/reductant methods within Ni-I/III cycles, the reaction steps that comprise a putative Ni-0/II C-N cross-coupling cycle for a thermally promoted catalyst system using organic amine base have not been elucidated. Here we disclose an efficient new nickel-catalyzed protocol for the C-N cross-coupling of amides and 2 '-(pseudo)halide-substituted acetophenones, for the first time where the (pseudo)halide is chloride or sulfonate, which makes use of the commercial bisphosphine ligand PAd2-DalPhos (L4) in combination with an organic amine base/halide scavenger, leading to 4-quinolones. Room-temperature stoichiometric experiments involving isolated Ni-0,Ni- I,Ni- and II species support a Ni-0/II pathway, where the combined action of DBU/NaTFA allows for room-temperature amide cross-couplings.

N(Alkyl)Carbonyl

SYNTHESIS-STUTTGART

This paper reports a room temperature, nickel-catalyzed Negishi cross-coupling of N-acylsuccinimides with arylzinc reagents via selective N-C bond cleavage enabled by amide bond twist. The reaction proceeds using a commercially available, air-stable Ni(II) precatalyst in the absence of additives under exceedingly mild conditions. Of broad interest, this report introduces N-acylsuccinimides as stable, crystalline, electrophilic, cost-effective, benign, amide-based acyl transfer reagents via acyl metal intermediates. The reaction selectivity is governed by half-twist of the amide bond in N-acylsuccinimides, thus opening the door for applications in metal-catalyzed manifolds via redox-neutral reaction pathways tuneable by amide bond distortion.

pyrrolidine-2,5-dione

Carbonyl

CHEMISTRY-A EUROPEAN JOURNAL

CHEMISTRY-A EUROPEAN JOURNAL

Xue, XS; Zhao, DB

The conventional oxidative Heck reaction between aryl boronic acids and alkenes typically involved the Pd-II/Pd-0/Pd-II catalytic cycle incorporating an external oxidant and often suffered C=C bond isomerization for internal alkyl-substituted alkenes via chain-walking. Herein, we demonstrate that the regioselectivity (gamma-selectivity vs. delta-selectivity) and pathway selectivity (hydroarylation vs. oxidative Heck coupling) of a directed Ni-catalyzed alkene arylation can be controlled by judicious tuning of the coordination environment around the nickel catalyst via optimization of an appropriate phosphine ligand and directing group. In this way, the Ni (0)-catalyzed oxidative Heck arylation that relies on transfer hydrogenation of an acceptor olefin is developed with excellent E/Z selectivity and regioselectivity. Mechanistic investigations suggest that the addition of the acceptor is crucial for lowering the energy for carbometalation and for enabling catalytic turnover.

CHEMISTRY-A EUROPEAN JOURNAL

A new method for the Suzuki-Miyaura cross-coupling of phenols and arylboronic acids through in situ phenol activation mediated by PyBroP is presented. The reaction proceeds efficiently by using cost-effective, markedly stable [NiCl2(dppp)] (dppp = 1,3-bis(diphenylphosphino) propane) as the catalyst in only 5 mol% loading, as well as in the absence of extra ligands. The method exhibits broad applicability and high efficiency towards a wide range of both phenols and boronic acids, including activated, nonactivated, deactivated, and heteroaromatic coupling partners. In addition, various functional groups, such as ether, amino, cyano, ester, and ketone groups, are compatible with this transformation. Notably, arylboronic acids containing an unprotected NH2 group and 2-heterocyclic boronic acids, which are generally problematic for coupling under conventional conditions, are also viable substrates, although moderate yields were obtained for sterically hindered substrates. Consequently, the in situ cross-coupling methodology coupled with the use of an inexpensive and stable nickel catalyst provides a rapid and efficient pathway for the assembly of biaryls and heterobiaryls with structural diversity from readily available phenol compounds.

ANGEW CHEM INT EDIT

While ketones are among the most versatile functional groups, their synthesis remains reliant upon reactive and low-abundance starting materials. In contrast, amide formation is the most-used bond-construction method in medicinal chemistry because the chemistry is reliable and draws upon large and diverse substrate pools. A new method for the synthesis of ketones is presented here that draws from the same substrates used for amide bond synthesis: amines and carboxylic acids. A nickel terpyridine catalyst couples N-alkyl pyridinium salts with in situ formed carboxylic acid fluorides or 2-pyridyl esters under reducing conditions (Mn metal). The reaction has a broad scope, as demonstrated by the synthesis of 35 different ketones bearing a wide variety of functional groups with an average yield of 60 +/- 16 %. This approach is capable of coupling diverse substrates, including pharmaceutical intermediates, to rapidly form complex ketones.

Triphenylpyridinium+BF4-

Carbonyl

CHEMISTRY-A EUROPEAN JOURNAL

Univ Sci & Technol China

CHEMISTRY-A EUROPEAN JOURNAL

OCO2Me

CHEMISTRY-A EUROPEAN JOURNAL

CHEM COMMUN

Despite the recent advance in C-H bond functionalization chemistry, the C-H bonds in the acridine ring system, which is an important scaffold in medicinal and material science, have met with limited success, due, in part, to the lack of activated C-H bonds adjacent to the ring nitrogen atom. Herein, several protocols that can effect the regioselective arylation and alkylation of acridines at the C-4 and C-9 positions are described.

CHEMISTRY-A EUROPEAN JOURNAL

ZnMe3Li2

Carpentier, JF

CHEMISTRY-A EUROPEAN JOURNAL

Direct amination of allylic alcohols with primary and secondary amines catalyzed by a system made of [Ni(1,5-cyclooctadiene)(2)] and 1,1'-bis(diphenylphosphino)-ferrocene was effectively enhanced by adding nBu(4)NOAc and molecular sieves, affording the corresponding allyl amines in high yield with high monoallylation selectivity for primary amines and high regioselectivity for monosubstituted allylic alcohols. Such remarkable additive effects of nBu(4)NOAc were elucidated by isolating and characterizing some nickel complexes, manifesting the key role of a charge neutral pentacoordinated eta(3)-allyl acetate complex in the present system, in contrast to usual cationic tetracoordinated complexes earlier reported in allylic substitution reactions.

N(Alkyl)Alkyl

CHEMISTRY-A EUROPEAN JOURNAL

Nickel-catalyzed selective cross-coupling of aromatic electrophiles (bromides, chlorides, fluorides and methyl ethers) with organolithium reagents is presented. The use of a commercially available nickel N-heterocyclic carbene (NHC) complex allows the reaction with a variety of (hetero)aryllithium compounds, including those prepared via metal-halogen exchange or direct metallation, whereas a commercially available electron-rich nickel-bisphosphine complex smoothly converts alkyllithium species into the corresponding coupled product. These reactions proceed rapidly (1h) under mild conditions (room temperature) while avoiding the undesired formation of reduced or homocoupled products.

CHEMISTRY-A EUROPEAN JOURNAL

An improved method for the reductive coupling of aryl and vinyl bromides with alkyl halides that gave high yields for a variety of substrates at room temperature with a low (2.5 to 0.5 mol%) catalyst loading is presented. Under the optimized conditions, difficult substrates, such as unhindered alkenyl bromides, can be coupled to give the desired olefins with minimal diene formation and good stereoretention. These improved conditions also worked well for aryl bromides. For example, a gram-scale reaction was demonstrated with 0.5 mol% catalyst loading, whereas reactions at 10 mol% catalyst loading completed in as little as 20 minutes. Finally, a low-cost single-component pre-catalyst, (bpy)NiI2 (bpy=2,2'-bipyridine) that is both air-and moisture-stable over a period of months was introduced.